Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai200237,China.
Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai200237,China.
J Chromatogr A. 2020 Aug 16;1625:461282. doi: 10.1016/j.chroma.2020.461282. Epub 2020 May 31.
In recent years, core-shell silica particles (CSSPs) have been increasingly used for highly efficient separation at fast flow rates and relatively low back pressures in high-performance liquid chromatography (HPLC). However, material synthesis techniques for producing CSSPs economically in batch processes remain elusive. In this report, a practical and straightforward method for the preparation of CSSPs is presented. By refluxing freshly prepared nonporous silica particles in ammonia-water solution in the presence of poly(diallyldimethylammonium chloride) at 70-100 °C, CSSPs with shell thicknesses of up to 300 nm and pore sizes from 8 to 25 nm were easily prepared. The effects of the synthetic conditions on the shell thickness, surface area, and pore size were investigated in detail, and the method reproducibility was evaluated in scale-up experiments. A mechanism of CSSP formation is also proposed. The CSSPs were characterized via scanning electron microscopy, transmission electron microscopy, laser particle size (dynamic light scattering) analysis, and nitrogen adsorption and desorption experiments. The synthesized 3.4-μm CSSPs were functionalized with dimethyloctadecylchlorosilane and used as an HPLC packing material, exhibiting excellent separation performance for both small molecules and large biomolecules. In summary, we report the simplest method developed thus far for the preparation of monodisperse core-shell silica particles suitable for HPLC column packing.
近年来，核壳型硅胶粒子（CSSP）已被越来越多地用于高效液相色谱（HPLC）中以实现快速流速和相对低背压下的高效分离。然而，在批处理过程中经济地生产 CSSP 的材料合成技术仍然难以实现。在本报告中，提出了一种实用且直接的制备 CSSP 的方法。通过在 70-100°C 下将新制备的无孔硅胶粒子在氨水溶液中回流，并存在聚二烯丙基二甲基氯化铵，可以轻松制备壳厚高达 300nm 且孔径为 8-25nm 的 CSSP。详细研究了合成条件对壳厚、表面积和孔径的影响，并在放大实验中评估了方法的重现性。还提出了 CSSP 形成的机理。通过扫描电子显微镜、透射电子显微镜、激光粒度（动态光散射）分析和氮气吸附和解吸实验对 CSSP 进行了表征。合成的 3.4μm CSSP 用二甲基十八烷基氯硅烷官能化，并用作 HPLC 填充材料，对小分子和大分子生物均表现出优异的分离性能。总之，我们报告了迄今为止开发的用于制备适用于 HPLC 柱填充的单分散核壳型硅胶粒子的最简单方法。
